Plakofuranolactone as a Quorum Quenching Agent from the Indonesian Sponge Plakortis cf. lita.

Valeria Costantino,Gerardo Della Sala,Rinat Bar-Shalom,Kumar Saurav,Alfonso Mangoni,Roberta Teta,Laura Steindler

doi:10.3390/md15030059

Valeria Costantino, Gerardo Della Sala + Show 5 more

Open Access

https://doi.org/10.3390/md15030059

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Abstract

There is an urgent need for novel strategies to fight drug resistance and multi-drug resistance. As an alternative to the classic antibiotic therapy, attenuation of the bacteria virulence affecting their Quorum sensing (QS) system is a promising approach. Quorum sensing (QS) is a genetic regulation system that allows bacteria to communicate with each other and coordinate group behaviors. A new γ-lactone that is capable of inhibiting the LasI/R QS system, plakofuranolactone (1), was discovered in the extract of the marine sponge Plakortis cf. lita, and its structure, including absolute configuration, was determined by NMR spectroscopy, MS spectrometry, and quantum-mechanical prediction of optical rotation. The quorum quenching activity of plakofuranolactone was evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075, E. coli pSB401, and C. violeaceum CV026) and was confirmed by measuring the total protease activity (a virulence factor which is under control of the LasI/R system) of the wild-type P. aeruginosa PAO1. Further research will be pursued to assess the potential of plakofuranolactone as a new antivirulence lead compound and a chemical tool to increase the knowledge in this field.

Highlights

The problem of antibiotic resistance, strictly connected to the large overuse of antibiotics in clinical practice and animal husbandry, is rising as a global emergency
Has been proposed as a potential therapeutic strategy for fighting detected in marine sponges and sponge isolates [16,17] and sponges appear as an attractive pathogens by attenuating the virulence effectors that are regulated by potential was attractive target to identify novel anti-virulence and Quorum sensing (QS)-inhibiting lead molecules
An in-depth re-examination of the organic extract of the Indonesian sponge Plakortis cf. lita was made in the search for novel bioactive lactones

Summary

Introduction

The problem of antibiotic resistance, strictly connected to the large overuse of antibiotics in clinical practice and animal husbandry, is rising as a global emergency. A recent pharmacological approach sources of antibacterial compounds [7,8].to control infections relies on studies performed on quorum sensing (QS), a mechanism of cell-cell and gene inare bacteria. Among others, acylated homoserine produce and whilst higher densities, the chemical accumulate accumulate andrelease once low theylevels reachofaAHLs, critical levelat(quorum) they interact with signals receptor proteins and Sponges appear as an quenching, has been proposed as a potential therapeutic strategy for fighting detected in marine sponges and sponge isolates [16,17] and sponges appear as an attractive pathogens by attenuating the virulence effectors that are regulated by potential was attractive target to identify novel anti-virulence and QS-inhibiting lead molecules. Structures of plakofuranolactone (1), three lactones isolated from marine genus Plakortis (2–4), and of penicillic acid (5). We report the structural elucidation of the lactone 1 and the evaluation of its QQ activity by in vitro assays

Results and Discussion

General Experimental Procedures

H NMR resolution

Dose Dependent QQ Assay

Inhibition of Virulence Factor Production—Pyocyanin and Protease

Conclusions